Impact of a leptin single nucleotide polymorphism and zilpaterol hydrochloride on growth and carcass characteristics in finishing steers

A total of 4,178 steers (mean initial BW = 403.9 ± 16.04 kg) were used to test the interactive effects, if any, of leptin R25C genotypes (CC, CT, or TT) and zilpaterol hydrochloride (ZH) feeding duration on growth performance and carcass traits. Steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens (90 steers/pen), and assigned randomly within genotype and block to 0 or 21 d of dietary ZH. All pens within a block were slaughtered on the same day (132.1 ± 10.9 d on feed). Final BW of steers fed ZH was 6.0 kg heavier (P = 0.008), and ZH-fed steers had greater (P = 0.003) ADG than steers not fed ZH. Feeding ZH decreased DMI in steers with increased frequency of the T allele (9.67, 9.53, and 9.28 kg/d for CC, CT, and TT, respectively), but DMI increased with the frequency of the T allele (9.68, 9.90, and 10.1 kg for CC, CT, and TT, respectively) when ZH was not fed (leptin genotype × ZH, P = 0.011). At the conclusion of the study, ultrasonic fat was greatest for TT steers (11.4 ± 0.28 mm) and least (P = 0.003) for CC steers (11.0 ± 0.25 mm). Regardless of ZH-feeding duration, TT steers produced a greater (P = 0.006) percentage of USDA yield grade (YG) 4 or higher carcasses (5.4 vs. 2.7%) and a lesser (P = 0.006) percentage of YG 1 carcasses (17.7 vs. 26.8%) than CC steers. In addition, ZH-fed steers produced a greater (P \u3c 0.001) percentage of USDA YG 1 carcasses (25.9 vs. 16.2%) and a lesser (P \u3c 0.001) percentage of YG 4 or higher carcasses (1.6 vs. 6.0%) than steers fed the control diet. Marbling scores and the percentage of carcasses grading USDA Choice and Prime were greater in TT than CC steers when fed diets devoid of ZH, but both marbling and quality grades did not differ among leptin genotypes when fed ZH for 21 d (leptin genotype × ZH, P ≤ 0.03). The amount of HCW gain tended to be less (P = 0.095) for steers of the TT genotype (12.7 kg) than either CC (16.3 kg) or CT (17.0 kg) genotypes. Results indicated that leptin R25C genotype impacted most traits associated with fatness whereas feeding ZH for 21 d affected HCW and ADG positively but impacted feed intake, marbling, and USDA quality grades negatively

Impact of a leptin single nucleotide polymorphism and zilpaterol hydrochloride on growth and carcass characteristics in finishing steers

A total of 4,178 steers (mean initial BW = 403.9 ± 16.04 kg) were used to test the interactive effects, if any, of leptin R25C genotypes (CC, CT, or TT) and zilpaterol hydrochloride (ZH) feeding duration on growth performance and carcass traits. Steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens (90 steers/pen), and assigned randomly within genotype and block to 0 or 21 d of dietary ZH. All pens within a block were slaughtered on the same day (132.1 ± 10.9 d on feed). Final BW of steers fed ZH was 6.0 kg heavier (P = 0.008), and ZH-fed steers had greater (P = 0.003) ADG than steers not fed ZH. Feeding ZH decreased DMI in steers with increased frequency of the T allele (9.67, 9.53, and 9.28 kg/d for CC, CT, and TT, respectively), but DMI increased with the frequency of the T allele (9.68, 9.90, and 10.1 kg for CC, CT, and TT, respectively) when ZH was not fed (leptin genotype × ZH, P = 0.011). At the conclusion of the study, ultrasonic fat was greatest for TT steers (11.4 ± 0.28 mm) and least (P = 0.003) for CC steers (11.0 ± 0.25 mm). Regardless of ZH-feeding duration, TT steers produced a greater (P = 0.006) percentage of USDA yield grade (YG) 4 or higher carcasses (5.4 vs. 2.7%) and a lesser (P = 0.006) percentage of YG 1 carcasses (17.7 vs. 26.8%) than CC steers. In addition, ZH-fed steers produced a greater (P \u3c 0.001) percentage of USDA YG 1 carcasses (25.9 vs. 16.2%) and a lesser (P \u3c 0.001) percentage of YG 4 or higher carcasses (1.6 vs. 6.0%) than steers fed the control diet. Marbling scores and the percentage of carcasses grading USDA Choice and Prime were greater in TT than CC steers when fed diets devoid of ZH, but both marbling and quality grades did not differ among leptin genotypes when fed ZH for 21 d (leptin genotype × ZH, P ≤ 0.03). The amount of HCW gain tended to be less (P = 0.095) for steers of the TT genotype (12.7 kg) than either CC (16.3 kg) or CT (17.0 kg) genotypes. Results indicated that leptin R25C genotype impacted most traits associated with fatness whereas feeding ZH for 21 d affected HCW and ADG positively but impacted feed intake, marbling, and USDA quality grades negatively

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke